THE ASSOCIATIONS OF SOCIOECONOMIC POSITION WITH STRUCTURAL BRAIN DAMAGE AND CONNECTIVITY AND COGNITION

Abstract Socioeconomic inequalities in the risk for cognitive impairment have been reported, which might partly act through structural brain damage and connectivity. This study investigated the extent to which the association of early-life socioeconomic position (SEP) with later-life cognitive performance is mediated by later-life SEP, and whether the association of SEP with later-life cognitive performance can be explained by structural brain damage and connectivity. We used cross-sectional data from the population-based Maastricht study (n=4,839; mean age 59.2±8.7 years, 49.8% women). Early-life SEP was assessed retrospectively by self-reported poverty and parental education. Later-life SEP included education, occupation, and household income. Participants underwent cognitive testing and 3 T magnetic resonance imaging to measure volumes of white matter hyperintensities, gray matter, white matter, cerebrospinal fluid, and structural connectivity. Multiple linear regression analyses tested the associations between SEP, MRI brain markers and cognition. Structural equation modeling tested mediation. Results indicated that higher SEP was associated with higher grey matter volume, lower white matter volume, and higher structural connectivity. Structural brain damage and lower structural connectivity were associated with lower cognition. Both higher early-life and later-life SEP were associated with higher cognition. The association of early-life SEP with later-life cognition was partly mediated by later-life SES (73.8%). However, the extent to which the association of SEP with cognition could be explained by structural brain damage or connectivity was marginal (up to 5.9%). More research is needed to investigate alternative pathways that can explain the associations between SEP with later-life cognition.

residence/segregation and income is employed in order to understand how disadvantage unfolded across the life course and into late life.The data come from 15 biographical interviews with older Roma living in rural and urban Romania, collected in 2021.Results illustrate how specific structural processes like sedentarization of nomad communities, the fall of the communist regime in 1989 and the retrocession of gold unevenly affected Roma across the intersectional characteristics and transformed into turning points in their lives, while interposing to a little extent with their pathways to social exclusion.De-institutionalized life courses and fast transitions had an important bearing on the ways disadvantage unfolded for older Roma living in segregated communities.Finally, super-linked lives at family and community level, when deprived of outside support, contributed to deep exclusion in later life.

THE SOCIAL DETERMINANTS OF BRAIN HEALTH: FROM THE SEARCH FOR MECHANISMS TO RECOMMENDATIONS TO INCREASE EQUITY
Chair: Anja Leist Co-Chair: Graciela Muniz-Terrera Dementia risk has been established to be partly attributable to modifiable social and behavioral risk factors.However, the biological pathways behind these associations and the effects of intervening on present risk factors to reduce dementia risk have not been fully elucidated.The symposium will present latest research on the social determinants of brain health and dementia.We will explore proposed mechanisms between modifiable risk factors and risk of dementia, and present findings on the modifiability of dementia risk through addressing risk factors.Specifically, the first presentation reports analyses testing possible pathways from socioeconomic status, notably childhood and adulthood indicators such as (parental) education and occupation, to cognitive functioning in later mid-adulthood via indicators of brain damage and white matter connectivity with the Maastricht Study.The second presentation reports empirical analyses testing the possible mediating role of the gut microbiome in the relationships between social and modifiable risk factors and Mild Cognitive Impairment with data of the controls of the Luxembourg Parkinson's Study.The third presentation reports on the associations between hearing loss as a modifiable risk factor and incident dementia in the UK Biobank and investigates the potential to modify hearing loss-associated dementia risk through the use of hearing aids.Lastly, the fourth presentation moves to recommendations for policy and government action.It gives an overview of various fields in which policy and legislation could implement cognitive impact assessments to protect individuals' cognition, with the aim of improving population brain health and health equity.This is a Brain Interest Group Sponsored Symposium.

THE ASSOCIATIONS OF SOCIOECONOMIC POSITION WITH STRUCTURAL BRAIN DAMAGE AND CONNECTIVITY AND COGNITION
Anouk Geraets 1 , Miranda Schram 2 , Sebastian Koehler 2 , Jacobus Jansen 2 , Martin van Boxtel 2 , Annemarie Koster 3 , Coen Stehouwer 2 , and Hans Bosma 2 , 1. University of Luxembourg,Luxembourg,2. Maastricht University Medical Centre+,Maastricht,Limburg,Netherlands,3. Maastricht University,Maastricht,Limburg,Netherlands Socioeconomic inequalities in the risk for cognitive impairment have been reported, which might partly act through structural brain damage and connectivity.This study investigated the extent to which the association of early-life socioeconomic position (SEP) with later-life cognitive performance is mediated by later-life SEP, and whether the association of SEP with later-life cognitive performance can be explained by structural brain damage and connectivity.We used cross-sectional data from the population-based Maastricht study (n=4,839; mean age 59.2±8.7 years, 49.8% women).Early-life SEP was assessed retrospectively by self-reported poverty and parental education.Later-life SEP included education, occupation, and household income.Participants underwent cognitive testing and 3 T magnetic resonance imaging to measure volumes of white matter hyperintensities, gray matter, white matter, cerebrospinal fluid, and structural connectivity.Multiple linear regression analyses tested the associations between SEP, MRI brain markers and cognition.Structural equation modeling tested mediation.Results indicated that higher SEP was associated with higher grey matter volume, lower white matter volume, and higher structural connectivity.Structural brain damage and lower structural connectivity were associated with lower cognition.Both higher early-life and later-life SEP were associated with higher cognition.The association of early-life SEP with later-life cognition was partly mediated by later-life SES (73.8%).However, the extent to which the association of SEP with cognition could be explained by structural brain damage or connectivity was marginal (up to 5.9%).More research is needed to investigate alternative pathways that can explain the associations between SEP with later-life cognition.

EDUCATION AS A RISK FACTOR OF MILD COGNITIVE IMPAIRMENT-THE ROLE OF THE GUT MICROBIOME
Matthias Klee 1 , Velma Aho 2 , Patrick May 2 , Rejko Krueger 2 , Paul Wilmes 2 , and Anja Leist 1 , 1. University of Luxembourg, Esch-sur-Alzette, Luxembourg, 2. Luxembourg Centre for Systems Biomedicine, Esch-Sur-Alzette, Luxembourg Background: Social determinants of health relate to an individual's risk of MCI and dementia.However, pathways from identified modifiable risk factors such as education are not well understood, yet.While previous findings suggest distinct taxonomic signatures of the gut microbiome in dementia and MCI patients, and further education linked to its composition, we sought to test the possibly mediating role of the gut microbiome in the relationship between education and MCI.Method: Gut microbiome composition was ascertained with 16S rRNA gene amplicon sequencing.MCI classification was based on the Montreal Cognitive Assessment.Education in years was grouped (0-10, 10-16, 16+).Mediation analysis was conducted decomposing direct and indirect effects of education on MCI mediated by gut microbiome diversity (Chao1, Inverse Simpson, Shannon) or individual species at Genus level (ldm-med, permanovamed).Differential abundance analysis across education groups was conducted (ANCOM-BC, DESeq2).Result: After exclusion of participants with PD, below age 50, or with missing data, n=256 participants (n=58 with MCI) of the Luxembourg Parkinson's Study were eligible for analysis (M[SD] Age=64.7[8.3]years).Education (16+ compared to 0-10 years of education) had a natural direct effect of NDE=0.36 (P<.01) on MCI, Chao1 included as mediator.We did not find significant mediation by gut microbiome composition or individual species.

Conclusion:
Our findings indicate direct effects of education not mediated by the gut microbiome.Taxonomic analysis suggests a signature linked to lower risk of dementia in higher educated individuals.Longitudinal research is needed to investigate associations over time.Age-related hearing loss is a predictor of cognitive impairment and dementia.The mechanisms of the observed associations are unclear but could involve depletion of cognitive reserve, the occupation of cognitive resources, and lack of sensory input to the brain.Hearing loss may therefore represent a preventable or treatable causative risk factor for dementia.Indeed, many studies report on lower rates of cognitive decline among hearing aid users when compared to non-users.However, most investigations to date have been observational or with relatively short follow-ups, thus precluding clear interpretations of the underlying mechanism.In our study using UK Biobank data with n=502,386 participants followed up from ~2008 to 2021, we emulate a randomised clinical trial to probe the role of initiating the use of hearing aids in people with conductive hearing loss or with self-reported hearing difficulties in the diagnosis dementia.Diagnosis of dementia was ascertained through hospital and death records, and selfreports in such a way as to increase the positive predictive value.Among participants with hearing loss or hearing difficulties, 2,914 (2.1%) were diagnosed with dementia, compared to 4,982 (1.4%) in those without hearing loss or hearing difficulties.Additional results on the relationship between hearing aid use and dementia, and stratified analyses by sex/gender and ethnicity will be presented.We discuss the modifiability of hearing loss and recommend studies with longer follow-ups to determine the efficacy of hearing loss interventions in reducing the risk of cognitive decline and dementia.